Despite the recent advances in the treatment for HIV/AIDS there remains a significant amount of variability in disease course that may be accounted for by psychosocial and psychobiological processes. This grant requests funding to determine the impact of both psychosocial (stress, coping and related variables) and biological factors (cortisol, Cytotoxic T lymphocytes, and NK#) on disease progression and mortality in HIV/AIDS. The study includes an HIV positive sample that has been followed for 3.5 years: This proposal would add new subjects comparable to the existing cohort and new biological measures and extend follow-up for 5 to 8 years total. At entry our subjects' CD4 counts were between 150 and 500, and they had never had serious AIDS symptoms (Category C). Particular strengths of the study that give this cohort the ability to contribute new information above other cohorts studied to date include (1) Our sample has diverse groups (28% women; 36% African American; 30% Hispanic). (2) The entire study has been conducted during the time protease inhibitors have been available, which makes issues such as adherence of paramount importance. Antiretroviral levels and genotyping will be added to ensure accuracy of adherence measures and to measure the development of resistance. (3) We have been able to quantify some relatively unexplored variables such as the doctor-patient relationship, spirituality, and emotional processing. (4) We are one of the first studies to be able to predict viral load. (5) We include several biological measures that could be investigated as both predictors and as mediators of disease progression. While we have strong cross sectional and longitudinal data showing that psychosocial variables are related to CD4 and viral load changes (controlling for relevant variables), the current long-term longitudinal design should allow us to relate these psychosocial variables to the development of serious AIDS symptoms and mortality. These analyses confirm that we have identified appropriate variables for expanding explorations of psychobiological links. Major strengths of the proposed study are that it will allow us to: (a) predict critical disease end points (e.g. Category C symptoms) and mortality; and (b) relate important psychosocial variables (e.g. stress, depression coping, adherence, doctor-patient relationship) to biological processes and disease endpoints. [unreadable] [unreadable]